Mechanisms of respiration and phosphorylation in Ascaris muscle mitochondria

In Ascaris muscle mitochondria the major respiratory chain-linked phosphorylation activity is accomplished by a NADH-linked reduction of fumarate to succinate. Oxygen can also be employed as a terminal electron acceptor via a cyanide- and salicyl-hydroxamate-resistant terminal oxidase. As in fumarate-dependent electron transport this process appears to be coupled to energy conservation at phosphorylation site I. The branchpoint from which electrons are taken from the main respiratory chain to either the alternative oxidase or fumarate reductase is likely to be on the oxygen side of the NADH dehydrogenase segment.Malate and succinate are the only substrates which appreciably support respiration in the mitochondrion of the nematode. Regardless of the presence or absence of oxygen malate is utilized by an oxidation-reduction reaction resulting in the formation of pyruvate, acetate, succinate, propionate and CO₂. In addition, aerobically, hydrogen peroxide is formed as the product of oxygen reduction. Succinate accumulation was found to be significantly higher in the anaerobic as compared to the aerobic incubation mixtures. This effect was accompanied by an increase in anaerobic malate consumption. ATP generation and the formation of pyruvate, acetate and propionate were found to be similar in the presence and absence of oxygen.In malate-supported respiration of intact Ascaris mitochondria reducing equivalents (NADH) are produced exclusively through pyruvate and acetate formation. These enzymatic reactions are functionally coupled to the electron transport-linked reductions of fumarate to succinate and oxygen to hydrogen peroxide, respectively. In accordance with the position of the redox potentials of the fumarate/succinate and O₂/H₂O₂ couples, anaerobic and aerobic respiration was found to be associated with relatively low energy conservation efficiencies. Thus one molecule of ATP was conserved per 2e^? transferred to fumarate or oxygen, respectively. No evidence could be obtained for a significant activity of energy conservation sites II and III and electron transfer through the alternative oxidase pathway was shown not to be coupled to phosphorylation.     

Carotid body oxygen consumption of the catin vitro

Summary The oxygen consumption of the cat carotid body has been measuredin vitro using a confinement method. The oxygen consumption of the organ appears to be very high (1.14 ml STPD·min^–1 per gram of dried tissue). The carotid body dry mass (0.044 mg) was much lower than the values found in the literature. The O₂ consumption versus O₂ tension relationship of this small organ shows no critical points as other organs generally do.A part of this work has been presented in a short note at the meeting of the Association des Physiologistes, June 1969. J. Physiol. (Paris)61, 339–340 (1969).     

Effects of aldosterone on lipid metabolism and renal oxygen consumption in the rat

Summary The plasma level of free fatty acids (FFA) in adrenalectomized rats increases by 50% after treatment with aldosterone (2 g/100 g rat).Lipolytic activity in peripheral fat tissue is lowered after adrenalectomy and doubles after in vivo administration of aldosterone to adrenalectomized rats (measured as free fatty acid release in vitro from epididymal fat tissue).Lypolysis of adipose tissue stimulated by the in vitro presence of ACTH also increases after in vivo administration of aldosterone.Incorporation of intravenously administered label from U¹⁴C-palmitate into total extractable lipid of renal tissue is augmented 3 h after aldosterone administration to adrenalectomized rats, while no increase of the radioactivity is observed in total lipid from liver tissue. Treatment with aldosterone does not affect the total lipid content of kidney or liver in adrenalectomized rats.The oxygen consumption rate of kidney cortex slices with lactate, -hydroxybuterate or acetoacetate as substrates is lowered after in vivo administration of aldosterone to adrenalectomized rats. With succinate, however, the respiratory rate of kidney slices increases after aldosterone treatment of adrenalectomized rats, the ouabain-sensitive respiration being more affected than the ouabain-insensitive respiration. An interpretation of the O₂ consumption data implicating competition of lipid metabolism for CoA-SH is discussed.     

Oxygen consumption of the isolated carotid body tissue (cat)

Summary The oxygen consumption of the isolated carotid body tissue measured in microchambers (volumes 12 and 20 μl) was 0.0051 μl O₂/mg wet weight min for an average of 54 measurements at 22±1°C, if the calculation was based on the oxygen pressure decrease of the surrounding medium measured polarographically in the range from 120 to 50 torr. It is bound to the presence of exogenous substrate and almost completely inhibited by antimycin but not significantly altered by addition of EGTA (4–16 mM) or Ca²⁺ (2mM). Measurements performed at higher oxygen pressures (300 to 100 torr) in the medium show that the oxygen consumption of isolated carotid body tissue is independent of oxygen pressure at these high oxygen pressures. The findings obtained under the above conditions argue in favor of a mitochondrial oxygen consumption. The results are discussed with regard to data obtained with needle electrodes in the perfused organ.     

The blood flow and oxygen consumption of brown adipose tissue in the new-born rabbit

1. A direct method for measuring venous outflow from brown adipose tissue in anaesthetized new-born rabbits is described.

2. During noradrenaline infusion the mean blood flow through brown adipose tissue increased from 87 to 360 ml./100 g tissue (wet wt.).min, and the mean rate of oxygen consumption of brown adipose tissue rose from 9·3 to 60 ml. O₂/100 g tissue.min.

3. During cold exposure the mean blood flow through brown adipose tissue increased from 90 to 304 ml./100 g tissue.min.

4. The mean cardiac output was 266 ml./kg body weight.min; during noradrenaline infusion it was 405 ml./kg body weight.min. At rest about one tenth, and during noradrenaline infusion about one quarter of the cardiac output went to brown adipose tissue.

5. It was calculated that most of the extra oxygen consumed during the metabolic response of the anaesthetized new-born rabbit to noradrenaline infusion or cold exposure was consumed by brown adipose tissue.

6. Hypoxia (breathing 10% O₂ in N₂) greatly reduced the increase in oxygen consumption but not the increase in blood flow in brown adipose tissue caused by noradrenaline infusion.

     

Maximum rate of oxygen consumption and quantitative histochemistry of succinate dehydrogenase in single muscle fibres ofXenopus laevis

Summary Three different types of single living muscle fibre were dissected from the iliofibularis muscle ofXenopus laevis. The fibres were mounted in a glass chamber and their rate of oxygen consumption was determined as a function of twitch frequency at 20 C. The rate of oxygen consumption increased with twitch frequency until it levelled off and reached a maximum. The maximum rate of oxygen consumption varied between fibres (0.019 to 0.161 nmol O₂ s^–1 mm^–3) and was reached at different twitch frequencies (<0.2 to 5.7 stimuli s^–1). After the determination of the maximum rate of oxygen consumption, the succinate dehydrogenase activity in cross sections of the fibre was determined by means of a quantitative histochemical method. A proportional relationship between the maximum rate of oxygen consumption and the succinate dehydrogenase activity was found. The maximum rate of oxygen consumption and the succinate dehydrogenase activity are also proportional to the volume density of mitochrondria in the three fibre types reported by Smith and Ovalle (1973;J. Anat., Lond. 116, 1–24). It is concluded that quantitative histochemistry of succinate dehydrogenase reliably predicts the maximum rate of oxygen consumption of muscle fibres inXenopus laevis and that the maximum rate of oxygen consumption of single muscle fibres is determined by the volume density of mitochondria.     

Metabolic properties of nerve endings isolated from rat brain

Energy metabolism was studied in nerve endings isolated from 3-week-old rat brain. Concentrations of glycogen, glucose, ATP, phosphocreatine and lactate were lower in synaptosomes than in the intact brain. The consumption of these endogenous substrates, the ability to generate high-energy phosphate, and the production of ammonia were determined in aerobic and anaerobic conditions. Unlike nerve tissue in general, synaptosomes preferentially utilized endogenous ATP and phosphocreatine stores which, on incubation in the absence of exogenous substrates, were emptied long before glycogen stores were exhausted. The optimal medium for respiratory studies was found to have electrolyte concentrations equal to the extracellular fluid. The synaptosomes had an endogenous respiration rate of 6.3 nmol O2 mg prot. min, measured with an oxygen electrode, and it probably reflects consumption of their glycogen stores. Glucose usually had no effect on the respiration rate of synaptosomes, but sometimes increased it slightly. However, after incubation in the presence of arsenate synaptosomes showed an increase in respiration when glucose was added. ADP, when added with glucose, also stimulated respiration. Pyruvate and succinate always increased respiration, succinate usually having the stronger effect. The present results show that isolated nerve endings are metabolically intact, which justifies their use in research on neurotransmission. In addition, opposite to the present consensus, synaptic transmission does not seem primarily to depend on the availability of glucose but rather on local stores of high-energy phosphate compounds.     

Sauerstoffverbrauch,Substrataufnahme und Lactatausscheidung von Dicrocoelium dendriticum (Trematoda)

Zusammenfassung Adulte Dicrocoelium dendriticum enthielten 8,6 mg Protein, 7,5 mg Kohlenhydrate (davon 5,7 mg Glykogen), 2,9 mg Lipide und 1,2 mg Asche pro 100 mg Frischgewicht. Die Atmung der intakten Parasiten wurde polarographisch und manometrisch gemessen. Die durchschnittliche Rate des endogenen Sauerstoffverbrauches betrug bei manometrischen Messungen 16,2 l O₂/mg N/Std. Dies entspricht einer Rate von 1,2 l O₂/mg Trockensubstanz/Std. Die Sauerstoffaufnahme der Parasiten war von der Sauerstoffspannung abhängig. Im Bereich zwischen 21 Vol.-% O₂ und 5% blieb die Rate annähernd konstant, sie war jedoch bei 100% deutlich erhöht und bei 2% signifikant vermindert.In manometrischen Versuchen bewirkte Glycerol (Endkonzentrationen 10 mM und 20 mM) eine deutliche Steigerung des Sauerstoffverbrauches, während Glucose, Galaktose und Fructose ohne Einfluß auf die Atmung blieben. In den polarographischen Untersuchungen war dagegen kein Effekt exogener Substrate zu erkennen. Einige der als Inhibitoren der Atmungskette in Säugetier-Mitochondrien bekannten Substanzen (2-Thenoyltrifluoraceton, 8-Hydroxychinolin, Salicylaldoxim, KCN und Antimycin A) verursachten eine deutliche Hemmung des Sauerstoffverbrauches. Die Rate des Sauerstoffverbrauches wurde durch 2,4-Dinitrophenol stimuliert, vermutlich infolge der Entkopplung der oxydativen Phosphorylierung. Glucose und Glycerol, einzeln in verschiedenen Konzentrationen zu zuckerfreier Tyrode-Lösung zugefügt, wurden von D. dendriticum unter aeroben oder anaeroben Bedingungen aufgenommen. Die Absorptionsraten waren mit den Substratkonzentrationen im Medium positiv korreliert. Aerob war die Substrataufnahme etwas höher als anaerob. Die Raten der Lactatausscheidung waren unter aeroben und anaeroben Bedingungen etwa gleich groß und unabhängig von den Substratkonzentrationen.

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Oxygen consumption, substrate absorption and lactate excretion of Dicrocoelium dendriticum (trematoda)

Summary Adult Dicrocoelium dendriticum contained 8.6 mg protein, 7.5 mg carbohydrates (including 5.7 mg glycogen), 2.9 mg lipids and 1.2 mg ash per 100 mg fresh weight.The respiration of intact parasites was studied by means of polarographic and manometric techniques. The average rate of the endogenous oxygen uptake determined manometrically was 16.2 l O₂/mg N/h. This corresponds with a value of 1.2 l O₂/mg dry substance/h. The respiration of the parasites responded to changes of the oxygen tension. The rate of oxygen consumption was nearly constant at oxygen tensions between 21 and 5 vol.-%, but it was significantly increased at 100% and deminished at 2%.Added glycerol (final concentrations of 10 mM and 20 mM) increased the rate of oxygen uptake in manometric experiments, whereas glucose, galactose and fructose produced no stimulatory effect. No influence of exogenous substrates was detectable in experiments using the polarographic technique.Some of the inhibitors of the respiratory chain in mitochondria of mammals (2-thenoyltrifluoroacetone, 8-hydroxyquinoline, salicylaldoxime, KCN, antimycin A) added to the media distinctly inhibited the oxygen consumption of D. dendriticum. The rate of respiration was increased by 2,4-dinitrophenol, probably due to the uncoupling of oxydative phosphorylation.Glucose or glycerol added separately to sugar-free Tyrode's solution at various concentrations was absorbed by D. dendriticum during aerobic and anaerobic conditions. The rates of absorption were positively correlated with the substrate concentrations in the medium. Glycerol was absorbed in larger amounts than glucose. The absorption of substrate was slightly higher under aerobic than under anaerobic conditions. The rates of lactate excretion were similar under aerobic and anaerobic conditions and independent of substrate concentrations.

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Herrn Prof. Dr. H. Spörri, Direktor des Veterinär-Physiologischen Institutes der Universität Zürich, zum 60. Geburtstag gewidmet.Mit Unterstützung durch den Schweizerischen Nationalfonds (Projekt Nr. 3. 140. 69).     

Action of bacterial lipopolysaccharide on the respiration of mouse liver mitochondria.

Escherichia coli O127:B8 lipopolysaccharide (LPS) inhibited oxygen consumption by isolated mouse liver mitochondria at 10 micrograms of LPS per mg of protein when glutamate + malate was the substrate and adenosine 5'-diphosphate had been added (state 3 respiration), but had little effect when adenosine 5'-diphosphate was not added (state 4 respiration). LPS stimulated state 4 respiration at 10 micrograms/mg of mitochondrial protein when succinate was the substrate but had little effect on state 3 respiration. Lipid A from Shigella sonnei at 2 micrograms/mg of mitochondrial protein also stimulated state 4 respiration but did not affect state 3 respiration with succinate as the substrate. Lipid A, unlike LPS, caused a decrease in the adenosine 5'-diphosphate/O ratio. LPS at 100 micrograms/mg of mitochondrial protein impaired the reduction of cytochromes aa3, c, and b when succinate was the substrate but not when reduced nicotinamide dinucleotide, dithionite, or glutamate was the substrate.     

Atmungsgrößen von Escherichia coli B/r and Bs1 und der Einfluß hoher UV-Dosen

Two very different radiation sensitive strains of Escherichia coli (B_/r and B_s1) showed only small differences of their rest metabolism. A significant distinction is to be seen some hours after separation of the bacteria from the nutrient substrate. There is a slow decrease of respiration intensity of the B_/r strain. The nucleoside adenosine which in buffer solution with glucose influenced only the B_/r cells increased the respiration rate of this strain on the same level as the B_s1 cells. Without glucose (endogenous respiration), the oxygen consumption of both strains is very small, but can be increased on the level of exogenous respiration by application of adenosine (5 × 10^?3 M). The small endogenous respiration is not decreased by high UV-doses; the glucose respiration after 80000 erg. mm^?2 falls to about 50% of the control. Adenosine can diminish this decline. These and other experiments showed an increase in the resistance to UV irradiation in the folllowing sequence: growth respiration in complete medium, glucose respiration in phosphate buffer, and endogenous respiration; the activity of metabolism falls in the same sequence. The different radiosensitivity of both bacterial strains may not be understood by their rest metabolism, which is very similar in both cases, except one suggests a multiplication of the small differences during the growth metabolism.     

Direct determination of local oxygen consumption of the brain cortex in vivo

Summary A method is described to determine local oxygen consumption quantitatively in the brain cortex under in vivo conditions. Local oxygen consumption is calculated from the slope of local tissue P_{O 2} decrease during a few seconds of total ischemia of the brain for each second after the stop of circulation. The decrease of tissue P_{O 2} is recorded simultaneously at several measuring sites. To be independent of oxygen chemically bound to hemoglobin, tissue P_{O 2} values are raised above 100 Torr. The calculation of local oxygen consumption for each second during the short period of ischemia showed that the O₂ consumption remains constant only for a few seconds ranging from 5 to maximally 15 s at different locations. Then O₂ consumption decreases continuously although the tissue P_{O 2} values are still above the full saturation of hemoglobin. The rate of local oxygen consumption varies considerably at different measuring sites of the superficial layers of the brain cortex (cat). The mean value amounts to 3±1.5 ml O₂/100 g tissue and minute.     

Examining the mechanisms responsible for lower ROS release rates in liver mitochondria from the long-lived house sparrow (Passer domesticus) and big brown bat (Eptesicus fuscus) compared to the short-lived mouse (Mus musculus)

Lower ROS release rate in long-lived species is likely caused by decreased reduction of electron transport chain (ETC) complexes, but how this is achieved remains largely unknown. We compared liver mitochondrial H₂O₂ release rates among endotherms of comparable size and metabolic rate: house sparrow and big brown bat (both long-lived) and house mouse (short-lived). We hypothesized that low ROS release rates in long-lived species result from (i) lower mitochondrial respiration rate, (ii) increased mitochondrial proton conductance (‘uncoupling to survive’), and/or (iii) increased ETC oxidative capacity (‘spare oxidative capacity’). H₂O₂ release rate was 70% lower in bats than mice despite similar respiration rates. Consistent with ‘uncoupling to survive’, proton leakiness was 3-fold higher in bats at membrane potentials above 130 mV. Basal H₂O₂ release rate and respiration rates were 2-fold higher in sparrows than mice. Consistent with ‘spare oxidative capacity’, subsaturating succinate decreased H₂O₂ release rate in sparrows but not mice. Moreover, succinate:Cytochrome c oxidoreductase activity was 3-fold higher in sparrows, and ETC inhibitors increased ROS release rate 20–27-fold in sparrows (with glutamate or subsaturating succinate) but only 4–5-fold in mice. Taken together these data suggest that complexes I and III are less reduced under physiological conditions in sparrows. We conclude that different long-lived species may use distinct mechanisms to lower mitochondrial ROS release rate.     

Succinate-dependent metabolism in Trypanosoma cruzi epimastigotes.

Trypanosoma cruzi epimastigotes permeabilized with digitonin (65 micrograms (mg protein)-1) to measure mitochondrial respiration were exposed to different substrates. Although none of the NADH-dependent substrates stimulated respiration, succinate supported not only oxygen consumption but also oxidative phosphorylation (respiratory control ratio of 1.9 +/- 0.3) indicating that the mitochondria were coupled. The rate of NADH-dependent oxygen consumption by membrane fractions (9.4 +/- 0.7 nmol min-1 (mg protein)-1) was reduced by 50% upon addition of catalase indicating that the electrons from NADH oxidation reduced oxygen to H2O2. NADH-dependent H2O2 production (16 +/- 1 nmol min-1 (mg protein)-1) was confirmed using cytochrome c peroxidase. This activity was inhibited by fumarate by 70%, suggesting a competition between fumarate and oxygen for the electrons from NADH, probably at the fumarate reductase level. The respiratory chain inhibitor antimycin blocked both respiration by intact cells and succinate-dependent cytochrome c by isolated membranes. No inhibition by antimycin was observed when NADH replaced succinate as an electron donor, indicating that the electrons from NADH oxidation reduced cytochrome c through a different route. Malonate blocked not only succinate-cytochrome c reductase and fumarate reductase, but also intact cell motility. These results suggest that succinate has a central role in the intermediate metabolism of i. cruzi, as it may be used for respiration or excreted to the extracellular space under anaerobic conditions. In addition, 2 potential sources of H2O2 were tentatively identified as: (a) the enzyme fumarate reductase; and (b) a succinate-dependent site, which may be the semiquinone form of Coenzyme Q9, as in mammalian mitochondria.     

Synergism of isothermal regimen and sodium succinate in experimental therapy of barbiturate coma

In rats with experimental thiopental coma rectal temperature decreased by 9.4°C, oxygen consumption 5-fold, and arteriovenous Po₂ gradient decreased 2-fold within 3 h; CO₂ accumulated in the blood and mixed type acidosis developed. Administration of sodium succinate under these conditions increased arteriovenous Po₂ gradient and reduced manifestations of metabolic acidosis. Maintenance of normal body temperature (warming) corrected primarily manifestations of respiratory acidosis. Each therapeutic agent reduced inhibition of O₂ consumption by 1/4; animal survival tended to increase from 42 to 50%. Combined use of these treatments potentiated the antiacidotic effect and increased survival to 92%. The authors conclude that hypothermia inhibits the therapeutic effect of succinate in barbiturate coma. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 7, pp. 66–69, July, 2006     

Oxygen Consumption of Ischaemic Rat Brain in vitro

Ischaemic brain injury was induced in rats and the oxygen consumption of brain homogenates was measured 1-4 hr afterwards.In animals with severe enough brain damage to produce fits in vivo, in vitro respiration was reduced below control values.Potentiation of oxygen uptake by ischaemic homogenates in vitro was produced by succinate, lactate, malate and adenosine diphosphate. Inhibition was produced by adenosine triphosphate. It is suggested that a deficiency of tricarboxylic acid intermediates contributes to the biochemical lesion in the ischaemic tissue, but there is no evidence of respiratory uncoupling.     

Michaelis-Menten kinetics model of oxygen consumption by rat brain slices following hypoxia

In the present study, we have measured partial pressure of oxygen (pO₂) profiles through rat brain slices before and after periods of hypoxia (5 and 10 min) to determine its effect on tissue oxygen demand. Tissue pO₂ profiles were measured through rat cerebral cortex slices superfused with phosphate buffer using oxygen (O₂)-sensitive microelectrodes at different times in controls [40% O₂ balance nitrogen (N₂)], and at different times before and after 5 or 10 min of hypoxia (100% N₂). A one-dimensional, steady-state model of ordinary diffusion with a Michaelis-Menten model of O₂ consumption where the maximal O₂ consumption (V_max) and the rate at half-maximal O₂ consumption (K_m) were allowed to vary was used to determine the kinetics of O₂ consumption. Actual pO₂ profiles through tissue were fitted to theoretical profiles by a least-squares method. V_max varied among penetrations in a control slice and among slices. V_max seemed to decrease after hypoxic insult, but the change was not statistically significant. The K_m value measured before hypoxia was lower than the first K_m value measured after the end of hypoxia, indicating that hypoxia induced a compensatory change in the metabolic state of the tissue. K_m increased immediately after both 5- and 10-min hypoxic insults and returned to normal after recovery for each case. It seems that during and immediately after short periods of hypoxia, K_m increases from near zero but returns to normal values within a few minutes.     

Effect of physical exercise on tissue respiration of endocrine glands

Summary A volumetric microrespirometer was used to investigate chages in the tissue respiration of the adrenals, thyroid and pituitary of rats after a single exhausting physical exercise. The animals were made to run on a treadmill for 90 min, that is, until they showed signs of fatigue.Oxygen uptake increased in the adrenals hy 39.1% but decreased in the thyroid by 51.9% and in the pituitary by 37.4%. It should be emphasized that the changes were statistically highly significant.The authors suppose that increased adrenal O₂ uptake may have been due to the stimulating influence of ACTH on the respiration processes in the cortex and intensification of oxidative processes in the medulla, and also increased blood supply in the entire organ during physical work.Diminished consumption of oxygen by the thyroid may have been caused by the inhibitory influence of factors connected with stress (the inhibitory influence of ACTH and corticosteroids, effort sympathicotonia, and increased body temperature).The decreased respiration of the pituitary is difficult to interpret but may have been caused by diminished blood supply and perhaps also an overheating of the organism.     

Oximetry with the NMR signals of hemoglobin Val E11 and Tyr C7

The NMR visibility of the signals from erythrocyte hemoglobin (Hb) presents an opportunity to assess the vascular PO₂ (partial pressure of oxygen) in vivo to gather insight into the regulation of O₂ transport, especially in contracting muscle tissue. Some concerns, however, have arisen about the validity of using the Val E11 signal as an indicator of PO₂, since its intensity depends on tertiary structural changes, in contrast to the quaternary structure changes associated with relaxed (R) and tense (T) transition during O₂ binding. We have examined the Val E11 and Tyr C7 signal intensity as a function of Hb saturation by developing an oximetry system, which permits the comparative analysis of the NMR and spectrophotometric measurements. The spectrophotometric assay defines the Hb saturation level at a given PO₂ and yields standard oxygen-binding curves. Under defined PO₂ and Hb saturation values, the NMR measurements have determined that the Val E11 signal, as well as the Tyr C7 signal, tracks closely Hb saturation and can therefore serve as a vascular oxygen biomarker.     

Coronary circulation response to hyperoxia after vagotomy and combined alpha and beta adrenergic receptors blockade in the anesthetized intact dog

Summary In closed-chest vagotomized dogs with alpha and beta adrenergic receptors blockade, ventilation with 100 per cent oxygen at atmospheric pressure did not modify the tension-time index nor the myocardial oxygen consumption. However, coronary blood flow decreased and coronary resistance increased significantly. A rise of the myocardialpO₂ was not likely to be primarily responsible for the elevation of the coronary resistance. Since in the presence of a fixed oxygen consumption the myocardialpO₂-elevation would occur following the rise of the arterialpO₂ whose direct effect on the vascular smooth muscle tone has been demonstratedin vitro by other workers, it may be concluded that elevation of arterialpO₂ exerted a direct constrictive action on the coronary vessels.However, oxygen transport to the left ventricle remained commensurate to the myocardial oxygen consumption. It is suggested that an additional mechanism adjusted the elevated coronary resistance. Shifts of the myocardialpO₂, resulting from transient imbalances between oxygen supply and demand, may be the stimulus initiating the adjustment through changing release of vasodilator or vasoconstrictor substances.Results of this paper and those previously published indicated that autonomic influences normally play a dominant role in the hyperoxia-induced reduction in cardiac work and metabolism.This investigation was supported in part by a grant from the Fonds National de la Recherche Scientifique of Belgium.A preliminary report on these results was made at the XXIV International Congress of Physiological Sciences, Washington, D.C., U.S.A., August 1968.     

Effects of exposure to hot environments on the regional distribution of blood flow and on cardiorespiratory function in sheep

Summary Sheep were exposed to thermoneutral conditions and then to either mild heat stress (40° C dry bulb/26° C wet bulb temperature) or to severe heat stress (42/39° C). The following measurements were made: regional distribution of cardiac output, deep body and skin surface temperatures, respiratory frequency, heart rate, blood pressure, cardiac output, oxygen consumption, haemoglobin concentration, theP _{CO 2},P _{O 2}, pH,S _{O 2} andC _{O 2} of arterial, mixed venous, dorsal sagittal sinus and transverse sinus blood. Body temperature and heart rate increased, and panting resulted in a marked respiratory alkalosis during severe heat stress, but otherwise, changes in gross cardiorespiratory functions were small. During both mild and severe heat stress approximately 11% of the cardiac output passed through arteriovenous anastomoses, compared with approximately 1.5% under thermoneutral conditions. Changes in blood flow to the skin, nasal mucosa and turbinates, tongue, heart, thyroids, adrenals, gut, spleen, kidneys, skeletal muscle, brain and spinal cord, illustrate a redistribution of cardiac output appropriate to combat the heat stress, but with probable influences of the respiratory alkalosis and alterations in local tissue metabolic rate.